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摘要
Background: External application of a Ca2+-mobilizing messenger, NAADP, to -cells activates intracellular Ca2+ changes and stimulates insulin secretion. Results: NAADP is transported into adipocytes and -cells in a glucose-dependent manner and is also released from pancreatic islets upon stimulation by high glucose. Conclusion: NAADP functions in an auto-/paracrine manner to regulate glucose homeostasis. Significance: NAADP can be exploited as a potential antidiabetic agent. @@@ Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger for mobilizing Ca2+ from intracellular stores in various cell types. Extracellular application of NAADP has been shown to elicit intracellular Ca2+ signals, indicating that it is readily transported into cells. However, little is known about the functional role of this NAADP uptake system. Here, we show that NAADP is effectively transported into selected cell types involved in glucose homeostasis, such as adipocytes and pancreatic -cells, but not the acinar cells, in a high glucose-dependent manner. NAADP uptake was inhibitable by Ned-19, a NAADP mimic; dipyridamole, a nucleoside inhibitor; or NaN3, a metabolic inhibitor or under Ca2+-free conditions. Furthermore, NAADP was found to be released from pancreatic islets upon stimulation by high glucose. Consistently, administration of NAADP to type 2 diabetic mice improved glucose tolerance. We propose that NAADP is functioning as an autocrine/paracrine hormone important in glucose homeostasis. NAADP is thus a potential antidiabetic agent with therapeutic relevance.
- 出版日期2013-12-6
- 单位北京大学深圳研究生院
